Multifaceted Interaction Between Hepatitis B Virus Infection and Lipid Metabolism in Hepatocytes: A Potential Target of Antiviral Therapy for Chronic Hepatitis B

Abstract

Hepatitis B virus (HBV) is considered a “metabolic virus” and affects many hepatic metabolic pathways. However, how HBV affects lipid metabolism in hepatocytes remains uncertain yet. Accumulating clinical studies suggested that compared to non-HBV-infected controls, chronic HBV infection was associated with lower levels of serum total cholesterol and triglycerides and a lower prevalence of hepatic steatosis. In patients with chronic HBV infection, high ALT level, high body mass index, male gender, or old age was found to be positively correlated with hepatic steatosis. Furthermore, mechanisms of how HBV infection affected hepatic lipid metabolism had also been explored in a number of studies based on cell lines and mouse models. These results demonstrated that HBV replication or expression induced extensive and diverse changes in hepatic lipid metabolism, by not only activating expression of some critical lipogenesis and cholesterolgenesis-related proteins but also upregulating fatty acid oxidation and bile acid synthesis. Moreover, increasing studies found some potential targets to inhibit HBV replication or expression by decreasing or enhancing certain lipid metabolism-related proteins or metabolites. Therefore, in this article, we comprehensively reviewed these publications and revealed the connections between clinical observations and experimental findings to better understand the interaction between hepatic lipid metabolism and HBV infection. However, the available data are far from conclusive, and there is still a long way to go before clarifying the complex interaction between HBV infection and hepatic lipid metabolism.

Metabolic Disorders in Patients with Chronic Hepatitis B Virus Infection: Coffee as a Panacea? (ANRS CO22 Hepather Cohort)

“…In terms of HBV-infected patients, a population prone to liver cancer, this possible lipid-raising effect is of particular interest. HBV infection is associated with lower levels of serum total cholesterol, HDL cholesterol, and TG [ 1 , 2 ]. Furthermore, lower serum cholesterol is associated with more advanced stages of liver disease in this population [ 9 , 59 ], while higher serum cholesterol is associated with better liver cancer survival [ 10 ].…”

“…Hepatitis B virus (HBV) infection affects hosts’ metabolic pathways. It is associated with lower levels of serum total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides (TG) [ 1 , 2 ]. Metabolic syndrome (MetS) is defined as having three or more of the following cardiovascular risk factors: central obesity, elevated TG, reduced HDL-cholesterol, elevated blood pressure, and elevated fasting glucose [ 3 ].…”

Construction, Identification and Analysis of the Interaction Network of African Swine Fever Virus MGF360-9L with Host Proteins

“…Subsequently, we verified the interaction between MGF360-9L and PSMA3, PSMC1, AMBRA1, and DDX20, a selected cellular protein related to cell metabolism [ 47 , 48 , 49 , 50 ], in vitro by co-immunoprecipitation and IFA. Many viruses, such as Hepatitis B Virus and SARS-CoV-2, hijack the metabolic processes of host cells to escape cellular defense or to acquire substances needed for replication [ 51 , 52 ]. GO, KEGG, and domain analyses of interacting proteins showed that MGF360-9L likely regulates host metabolic response during ASFV infection.…”

PPAR Ligands Induce Antiviral Effects Targeting Perturbed Lipid Metabolism during SARS-CoV-2, HCV, and HCMV Infection

“…While lipids and their receptors are key players in the early stages of HCV infection, molecules targeting lipids or their receptors could be considered as novel strategies against HCV infection, by preventing or limiting virus-induced damages [ 47 ]. Likewise, HCV, hepatitis B virus (HBV), is considered a metabolic virus, as it affects many hepatic metabolic pathways [ 48 ]. Several studies based on cell lines and mouse models explored the mechanisms by which HBV infection affects lipid metabolism but, to date, results are not conclusive.…”